Tissue engineering describes an attempt to create tissues that repair or replace damaged tissues, typically by combining the use of biomaterials and cells. Control of polymer scaffold architecture is of fundamental importance in tissue engineering A wide variety of techniques for controlling the architecture of biomaterials are already available for relatively large feature sizes of the order of millimeters to centimeters. These include polymer extrusion, solution casting and particulate leaching, deposition of a polymer solution stream on a spinning mandrel and manipulation of sheets of polymer meshes. To achieve arbitrary three-dimensional geometries, preformed sheets of biomaterial have been cut and laminated with a resolution of 0.5 mm. Such supports are useful for forming the macroscopic shape of the replacement tissue (i.e. an ear for cartilage tissue engineering) or for customizing tissues replacements for individualized patients (i.e. an eye socket for bone tissue engineering).
To manipulate scaffold architecture on smaller length scales, many different microfabrication techniques have been developed in recent years, each with its own intrinsic limits related to the materials employed, its resolution or its costs. Injection molding against a microfabricated silicon template was utilized by Kapur et al (1996) with a resolution of 10 microns. In addition, a three dimensional printing technique developed by Griffith et al (1998) utilizes a polymer powder spread on a plate. Three dimensional structures are achieved by application of a solvent binder (e.g. chloroform) through an ink-jet head (Shastri et al., 2000). The resolution of this method is dependent upon the polymer particle size where the typical features are on the order of 300 microns. These techniques are useful for forming complex tissues such as bone/cartilage composites for the knee and for optimizing microscale architecture to improve the function of the resultant tissue. For example, scaffold texture can alter cell migration, ingrowth, vascularization, and host integration. Microscale scaffold architecture can also modify the cellular responses such as growth and differentiation as has been shown on three-dimensional polymer meshes (e.g. U.S. Pat. No. 5,443,950) Many of the techniques described above require processing conditions such as heating and polymer grinding that may be limiting for the inclusion of bioactive moieties or high resolution features, respectively.
Methods to prepare scaffolds with microscale structure that are more amenable to use with biodegradable polymers such as poly-DL-lactide-co-glycolide (PLGA) have also been developed. Material microstructure was first controlled by process parameters such as the choice of solvent in phase separation, doping with particulate leachants, gas foaming, woven fibers, and controlled ice crystal formation and subsequent freeze-drying to create pores; however, these scaffolds lack a well-defined organization that is found in most tissues in vivo (i.e. pores are randomly distributed rather than oriented and organized in functional units).
At the microscale, techniques to control the architecture of biodegradable polyester scaffolds, such as poly(DL-lactide-co-glycolide) (PLGA), are being developed and described in the literature. For example, a Fused Deposition Modelling (FDM) method can create solid objects with ˜250 micron resolution using a robotically controlled miniature extruder head (Zein et al, 2000). Biodegradable polymer membranes of thickness between 500 and 2000 microns cut by laser can be laminated to produce structures with 100 micron resolution (Mikos et al., 1993). By exploiting computer-aided design and solid free form fabrication, both three-dimensional printing and lost mold methods have been developed. Three dimensional printing employs polyester particles that are bound together by the application of chloroform from an inkjet head with a resolution of approximately 300 microns (Mrksich et al., 1997). Similarly, the lost mold technique uses stereolithography to fabricate an epoxy mold that is lost when the surrounding ceramic is heated, with a resolution of approximately 450 microns (Chu et al, 2002). Although complex objects can be created using these various technologies, the ability to reproducibly and simply fabricate polyester scaffolds with organized, arbritarily-oriented tissue-scale features (i.e. 10-100 microns) has not been reported.